ad The hibernating 100S complex is a target of ribosome-recycling factor and elongation factor G in Staphylococcus aureus [Protein Synthesis and Degradation] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The formation of translationally inactive 70S dimers (called 100S ribosomes) by hibernation-promoting factor is a widespread survival strategy among bacteria. Ribosome dimerization is thought to be reversible, with the dissociation of the 100S complexes enabling ribosome recycling for participation in new rounds of translation. The precise pathway of 100S ribosome recycling has been unclear. We previously found that the heat-shock GTPase HflX in the human pathogen Staphylococcus aureus is a minor disassembly factor. Cells lacking hflX do not accumulate 100S ribosomes unless they are subjected to heat exposure, suggesting the existence of an alternative pathway during nonstressed conditions. Here, we provide biochemical and genetic evidence that two essential translation factors, ribosome-recycling factor (RRF) and GTPase elongation factor G (EF-G), synergistically split 100S ribosomes in a GTP-dependent but tRNA translocation-independent manner. We found that although HflX and the RRF/EF-G pair are functionally interchangeable, HflX is expressed at low levels and is dispensable under normal growth conditions. The bacterial RRF/EF-G pair was previously known to target only the post-termination 70S complexes; our results reveal a new role in the reversal of ribosome hibernation that is intimately linked to bacterial pathogenesis, persister formation, stress responses, and ribosome integrity. Full Article
ad The streptococcal multidomain fibrillar adhesin CshA has an elongated polymeric architecture [Microbiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 The cell surfaces of many bacteria carry filamentous polypeptides termed adhesins that enable binding to both biotic and abiotic surfaces. Surface adherence is facilitated by the exquisite selectivity of the adhesins for their cognate ligands or receptors and is a key step in niche or host colonization and pathogenicity. Streptococcus gordonii is a primary colonizer of the human oral cavity and an opportunistic pathogen, as well as a leading cause of infective endocarditis in humans. The fibrillar adhesin CshA is an important determinant of S. gordonii adherence, forming peritrichous fibrils on its surface that bind host cells and other microorganisms. CshA possesses a distinctive multidomain architecture comprising an N-terminal target-binding region fused to 17 repeat domains (RDs) that are each ∼100 amino acids long. Here, using structural and biophysical methods, we demonstrate that the intact CshA repeat region (CshA_RD1–17, domains 1–17) forms an extended polymeric monomer in solution. We recombinantly produced a subset of CshA RDs and found that they differ in stability and unfolding behavior. The NMR structure of CshA_RD13 revealed a hitherto unreported all β-fold, flanked by disordered interdomain linkers. These findings, in tandem with complementary hydrodynamic studies of CshA_RD1–17, indicate that this polypeptide possesses a highly unusual dynamic transitory structure characterized by alternating regions of order and disorder. This architecture provides flexibility for the adhesive tip of the CshA fibril to maintain bacterial attachment that withstands shear forces within the human host. It may also help mitigate deleterious folding events between neighboring RDs that share significant structural identity without compromising mechanical stability. Full Article
ad The major subunit of widespread competence pili exhibits a novel and conserved type IV pilin fold [Protein Structure and Folding] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Type IV filaments (T4F), which are helical assemblies of type IV pilins, constitute a superfamily of filamentous nanomachines virtually ubiquitous in prokaryotes that mediate a wide variety of functions. The competence (Com) pilus is a widespread T4F, mediating DNA uptake (the first step in natural transformation) in bacteria with one membrane (monoderms), an important mechanism of horizontal gene transfer. Here, we report the results of genomic, phylogenetic, and structural analyses of ComGC, the major pilin subunit of Com pili. By performing a global comparative analysis, we show that Com pili genes are virtually ubiquitous in Bacilli, a major monoderm class of Firmicutes. This also revealed that ComGC displays extensive sequence conservation, defining a monophyletic group among type IV pilins. We further report ComGC solution structures from two naturally competent human pathogens, Streptococcus sanguinis (ComGCSS) and Streptococcus pneumoniae (ComGCSP), revealing that this pilin displays extensive structural conservation. Strikingly, ComGCSS and ComGCSP exhibit a novel type IV pilin fold that is purely helical. Results from homology modeling analyses suggest that the unusual structure of ComGC is compatible with helical filament assembly. Because ComGC displays such a widespread distribution, these results have implications for hundreds of monoderm species. Full Article
ad Radical new business model for pharmaceutical industry needed to avert antibiotic resistance crisis By feedproxy.google.com Published On :: Mon, 12 Oct 2015 09:19:24 +0000 7 October 2015 20151009Antibiotics.jpg High-level complex of physiologically active antibiotic substance extracted from blastema at the Arctic Innovation Center (AIC) of Ammosov, North-Eastern Federal University (NEFU) in Yakutsk. Photo: Yuri Smityuk/ITAR-TASS Photo/Corbis. Revenues for pharmaceutical companies need to be 'delinked' from sales of antibiotics to avoid their over-use and avert a public health crisis, says a new report from the think-tank Chatham House.Over-use of antibiotics is contributing to the growing resistance of potentially deadly bacteria to existing drugs, threatening a public health crisis in the near future. The report notes that, by 2050, failing to tackle antibiotic resistance could result in 10 million premature deaths per year. Novel antibiotics to combat resistant pathogens are thus desperately needed, but market incentives are exacerbating the problem. Towards a New Global Business Model for Antibiotics: Delinking Revenues from Sales states that, 'The current business model requires high levels of antibiotic use in order to recover the costs of R&D. But mitigating the spread of resistance demands just the opposite: restrictions on the use of antibiotics.' To tackle this catch-22 problem, the Centre on Global Health Security at Chatham House recommends the establishment of a global body to implement a radical new business model for the industry, which would encourage investment and promote global access to - and conservation of - antibiotics. The current business model has several perverse effects. As R&D is an inherently risky and costly endeavour, the industry is chronically under-investing in new treatments. Today, few large pharmaceutical companies retain active antibacterial drug discovery programmes. Re-stoking the industry's interest in antibiotics would be one of the primary roles of the new body. Secondly, the need to recover sunk cost under the current business model encourages both high prices and over-marketing of successful drugs, making potentially life-saving treatments unaffordable to many in developing countries, while simultaneously encouraging over-use in developed markets and increasing resistance. The new global body would address these challenges by ‘delinking’ pharmaceutical revenues from sales of antibiotics. It would do this by directly financing the research and development of new drugs, which it would then acquire at a price based on production costs rather than the recovery of R&D expenses. Acquisition could take the form of procurement contracts with companies, the purchase of full IP rights or other licensing mechanisms. This would enable it to promote global access to antibiotics while simultaneously restricting over-use. Conservation would be promoted through education, regulation and good clinical practice, with the report recommending that 'proven conservation methods such as antibiotic stewardship programmes… be incentivized and implemented immediately.'Priorities for R&D financing would be based on a comprehensive assessment of threats arising from resistance. Antibiotics would qualify for the highest level of financial incentives if they combat resistant pathogens posing a serious threat to human health. Finance for the new body would come from individual nation states, with the report noting that this could 'begin with a core group of countries with significant research activity and large antibiotic markets, (though) it is envisaged that all high income countries should make an appropriate financial contribution.' It is not yet clear exactly how much funding would be necessary to combat resistance, but with inaction expected to cost $100 trillion in cumulative economic damage, the report argues that 'an additional global investment of up to $3.5 billion a year (about 10 per cent of the current value of global sales of antibiotics) would be a bargain.' Editor's notes Towards a New Global Business Model for Antibiotics: Delinking Revenues from Sales, is a Chatham House report edited by Charles Clift, Unni Gopinathan, Chantal Morel, Kevin Outterson, John-Arne Røttingen and Anthony So.The report is embargoed until 00.01 GMT Friday 9 October.For more information, or to request an interview with the editors, contact the press office. Contacts Press Office +44 (0)20 7957 5739 Email Full Article
ad By enabling formal trade, Nigeria can unleash its vast potential By feedproxy.google.com Published On :: Mon, 07 Dec 2015 16:18:19 +0000 3 December 2015 20151207Nigeriabooming.jpg Nigeria’s booming informal trade is costly for society, business and government, yet a critical opportunity exists to formalize such trade and drive more sustainable and less volatile growth, argues a new report from Chatham House.According to one estimate, informal activity accounts for up to 64 per cent of Nigeria’s GDP. Nigeria's Booming Borders: The Drivers and Consequences of Unrecorded Trade finds that this is a result of obstacles that impede trading through formal channels. These drivers include bureaucratic burdens and other factors, such as:The need for Nigerian businesses to produce at least nine documents in order to send an export shipment and at least 13 in order to bring in an import consignment.Rigid and dysfunctional foreign-exchange regulations that push most smaller traders into the incompletely regulated parallel exchange market.Corruption and unofficial ‘taxation’, especially on major border highways, which delegitimize formal channels and encourage the use of smuggling routes.As a result, the state loses direct tax revenues that would be generated by formal cross-border trade. This is not just siphoned into the informal economy; some is lost entirely. For example, many shippers opt to dock in neighbouring countries rather than deal with the expense and difficulty of using Nigeria’s ports.Informal trade also undermines the social contract between the private sector and government. The state lacks tax revenues to pay its officials, improve infrastructure or implement reforms, while traders feel the government provides no services in return for any taxes they might pay.‘Every day tens of thousands of unofficial payments are made, none destined for the government. Policy-makers need to create an environment that encourages trade to flow through formal channels and capture lost revenue’, says co-author Leena Koni Hoffmann.‘Formalization would assist Nigeria to pursue more high-quality, high-tech economic activity at a time when rising labour costs in Asia are creating scope for Nigerian manufacturers to compete’, she adds.The report makes a number of recommendations for how Nigeria could encourage more formal trade, including:Strengthening the resources and capacity of the Federal Ministry of Industry, Trade and Investment to coordinate action across key government ministries, departments and agencies, as well as public and private stakeholders.Prioritizing engagement in the development of Economic Community of West African States (ECOWAS) trade policies and fully implementing the ECOWAS Protocol on Free Movement of Persons to reduce harassment at borders.Allowing banks to operate simple services for small and medium-sized businesses to make trade payments directly from Nigerian naira to CFA francs and vice versa.Improving basic facilities that support traders, including improving the efficiency of border posts, installing truck parks and all-weather surfacing on market access roads, and introducing online booking for trucks to enter ports.Separating responsibilities for assessing duty and tariff liabilities from revenue collection in order to reduce opportunities for corruption, an approach already tested with success by the Lagos State Internal Revenue Service.Increasing funding and technical support for the National Bureau of Statistics, which has a significant role to play in measuring and capturing more of Nigeria’s external trade.Interviews conducted for the report reveal that business people would welcome the opportunity to pay taxes, but only if they received assurance that these payments would represent a contract with government guaranteeing that conditions for business would be improved.‘As Africa’s largest economy, formalizing external trade would allow Nigeria to fulfil its potential as the trading engine of the West and Central African economy and shape the business landscape across the region,’ says co-author Paul Melly. Editor's notes Read Nigeria's Booming Borders: the Drivers and Consequences of Unrecorded Trade (embargoed until 17:00 GMT on Monday 7 December).To request an interview with the authors, contact the press office.Nigeria’s recorded external trade for 2014 was $135.8 billion.Estimate of informal activity as a percentage of GDP from Jonathan Emenike Ogbuabor and Victor A. Malaolu, ‘Size and Causes of the Informal Sector of the Nigerian Economy: Evidence from Error Correction Mimic Model’, Journal of Economics and Sustainable Development, Vol. 4, No. 1, 2013. Contacts Press Office +44 (0)20 7957 5739 Email Full Article
ad Dr Lina Khatib to head Middle East and North Africa Programme By feedproxy.google.com Published On :: Tue, 03 May 2016 12:55:52 +0000 3 May 2016 Chatham House is pleased to announce that Dr Lina Khatib has joined the institute as head of the Middle East and North Africa Programme. Dr Lina Khatib takes up her role at Chatham House as of 3 May 2016. She joins Chatham House from her position as a senior research associate with the Arab Reform Initiative. Previously, she was director of the Carnegie Middle East Center in Beirut and, prior to that, the co-founding head of the Program on Arab Reform and Democracy at Stanford University’s Center on Democracy, Development, and the Rule of Law.Dr Robin Niblett, director of Chatham House, said: ‘I take great pleasure in welcoming Dr Lina Khatib to Chatham House. Dr Khatib joins our team at a critical time of prolonged turmoil and upheaval in the Middle East and North Africa. Her significant international experience of analysing developments in the region will be a great asset to Chatham House as it assesses the core political, economic, societal and security issues affecting peace and prosperity across this region. I would also like to thank Dr Neil Quilliam for his strong leadership of the Middle East and North Africa Programme since 2014.’Dr Lina Khatib, said: ‘At a time when countries in the Middle East and North Africa face critical challenges, from continuing conflicts in Syria, Libya, and elsewhere, to increasing socio-economic pressures, it is essential for policy decisions to be informed by rigorous and forward-thinking research and debate. I look forward to working with the team at Chatham House to assist decision-makers and the public in understanding the complexities of an important region at this turbulent moment and seeking creative ways of alleviating its challenges.’ Dr Neil Quilliam, who has been acting head of the programme since December 2015, will continue with his role as senior research fellow and Syria project director. Editor's notes Dr Khatib holds a BA from the American University of Beirut and an MA and PhD from the University of Leicester. Her research spans the international relations of the Middle East, Islamist groups, political transitions and foreign policy, with a focus on the regional and international political and security dimensions of the Syrian conflict.Dr Khatib has published seven books, including Image Politics in the Middle East: The Role of the Visual in Political Struggle (I. B. Tauris, 2013), Taking to the Streets: The Transformation of Arab Activism (co-edited with Ellen Lust, Johns Hopkins University Press, 2014), and The Hizbullah Phenomenon: Politics and Communication (co-authored with Dina Matar and Atef Alshaer, Hurst/Oxford University Press, 2014). She has also published widely on public diplomacy, political communication, and political participation in the Middle East.Since 2008, Dr Khatib has been a founding co-editor of the Middle East Journal of Culture and Communication and a research associate at the University of London’s School of Oriental and African Studies. From 2010 to 2012, she was a non-resident research fellow at the University of Southern California’s Center on Public Diplomacy. She lectured at Royal Holloway, University of London from 2003 to 2010.Prior to joining the academic field, Dr Khatib worked in broadcast journalism in Lebanon. Full Article
ad John Kerry and Mohammad Javad Zarif named winners of the Chatham House Prize 2016 By feedproxy.google.com Published On :: Mon, 24 Oct 2016 12:40:51 +0000 24 October 2016 US Secretary of State John Kerry and Iranian Minister of Foreign Affairs Dr Mohammad Javad Zarif have been voted as the winners of this year’s Chatham House Prize. 2016-CHPrize-Kerry-ZarifA.jpg The Chatham House Prize is presented annually to the person, persons or organization deemed by members of the Royal Institute of International Affairs to have made the most significant contribution to the improvement of international relations in the previous year.This year, members voted for John Kerry and Mohammad Javad Zarif in recognition of their crucial roles, throughout 2015, in successfully negotiating the historic nuclear deal between Iran and the P5+1 – considered to be one of the most intractable diplomatic stand-offs in international affairs in the 21st century.The deal was one that many thought impossible. Overcoming enormous technical complexity, entrenched domestic opposition in the United States and Iran and three decades of intense hostility between their two countries, Kerry and Zarif’s leadership and commitment, in particular, were imperative to sustaining and driving the negotiations to their successful conclusion. With the vital participation of officials from other permanent members of the UN Security Council, Germany and the EU, they secured a deal, endorsed by the UN Security Council and more than 90 countries, which was a victory for diplomacy as well as against nuclear proliferation.EventsJohn Kerry at Chatham House: Chatham House Prize Presentation31 October 2016Mohammad Javad Zarif at Chatham House: Overcoming Regional Challenges in the Middle East4 February 2016NomineesThe nominees for the Chatham House Prize 2016 were:Laurent Fabius, Minister of Foreign Affairs, France (2012–16) and Christiana Figueres, Executive Secretary, UN Framework Convention Attahiru Muhammadu Jega, Chairman, Independent National Electoral Commission, Nigeria (2010–15)John Kerry, US Secretary of State and Dr Mohammad Javad Zarif, Iran’s Minister of Foreign AffairsAbout the Chatham House PrizeThe Chatham House Prize is presented to the person, persons or organization deemed by members of Chatham House to have made the most significant contribution to the improvement of international relations in the previous year.The selection process is independent, democratic and draws on the deep knowledge of Chatham House's research teams, making the Prize a distinctive and unique award in the field of international affairs.A short-list of nominees is selected by the institute's three presidents from a longer list submitted by the research programmes and departments in their areas of expertise. The recipient is then determined by Chatham House's broad membership base on a one-member, one-vote basis. The award is presented on behalf of the institute's patron, Her Majesty the Queen, representing the non-partisan and authoritative character of the Prize.The Chatham House Prize was launched in 2005. Previous recipients of the Prize include Burmese democracy campaigner Aung San Suu Kyi, Médecins Sans Frontières, former US Secretary of State Hillary Clinton, and Melinda Gates, co-founder of the Bill and Melinda Gates Foundation.For more information, please contact: Jenny Williams, Media Relations ManagerEmail: jwilliams@chathamhouse.orgPhone: +44 (0) 7921 867 626 Full Article
ad Chatham House appoints Adam Ward as deputy director By feedproxy.google.com Published On :: Mon, 16 Jan 2017 14:54:55 +0000 17 January 2017 Chatham House is pleased to announce that Adam Ward will join the institute in a new role as deputy director. 2017-01-17-AdamWard2.jpg Adam Ward takes up the position of deputy director on 10 April 2017 and will join Chatham House from the International Institute of Strategic Studies (IISS) in London, where he has served as director of studies since 2009.As deputy director, Adam will oversee and coordinate Chatham House's multiple areas of research, help manage the institute's relationships with key external constituencies, ensure the delivery of high-quality publications and deputize for the institute’s director, Dr Robin Niblett.This is a new position, created after a period of sustained growth for Chatham House, especially in research and policy outputs. The appointment also coincides with the opening this spring of new working and meeting space for the institute in Ames House, the building adjacent to Chatham House on Duke of York Street in the St James's area of central London.At IISS, publishers of the renowned annual Military Balance and other high-quality publications and organizers of influential annual security summits, including the Shangri-La Dialogue, Adam was responsible for the oversight of its worldwide research activities, which are also conducted from IISS offices in the Middle East, Asia and the US. Adam led the establishment of the office in Washington and was previously a senior fellow for East Asia.Dr Robin Niblett, director of Chatham House, said:‘I am delighted that Adam Ward will shortly be joining Chatham House. At a time of great uncertainty and risk in international affairs, his experience in leading research at the prestigious IISS and knowledge of how research institutes can develop and communicate their ideas on public policy will be of enormous value. His wide-ranging expertise on geopolitics and the foreign policies of China and the United States will also help the institute develop integrated projects that reflect the changing balance of world power. I very much look forward to working with him.’Adam Ward said:‘I am excited to take up this opportunity to join Chatham House's executive leadership and to work with Robin Niblett and his senior management team. Chatham House has a well-deserved reputation for rigour and excellence in its research and for providing insights and solutions across a comprehensive range of international challenges. Chatham House's capacity for inter-disciplinary research is one of its distinctive strengths, and I look forward to ensuring its ideas are brought to bear on an ever more complex policy environment.’ Editor's notes About Chatham HouseChatham House, the Royal Institute of International Affairs, is an independent policy institute based in London. Its mission is to help build a sustainably secure, prosperous and just world. Founded in 1920, Chatham House engages governments, the private sector, civil society and its members in open debate and confidential discussion on the most significant developments in international affairs. Each year, the institute runs more than 300 private and public events – conferences, workshops and roundtables – in London and internationally with partners. Its convening power attracts world leaders and the best analysts in their respective fields from across the globe.About Adam WardAs director of studies of the IISS, Adam Ward has since 2009 led the execution of the Institute’s worldwide research activities, including setting priorities, raising funds and the management of a research staff distributed across four international offices. Between 2009 and 2014 he organized the annual series of IISS Global Strategic Review conferences. He represents the institute internationally among its audiences in government, the expert community and business.Adam was previously, from 2006, executive director of the IISS office in Washington DC, where he led the relocation of the office to larger premises, an expansion in its staff, the development of a busy events programme and research activities and acted as the institute’s principal liaison with US government agencies and the Washington-based diplomatic and academic community. Prior to this, he served from 2001 simultaneously as the IISS senior fellow for East Asian security and editor of Strategic Comments, a series of analytical briefing papers on global topics.He began his career in 1997 as an analyst and editor at the consulting firm Oxford Analytica, focusing on the Asia-Pacific region. He holds a bachelor’s degree in German and Politics and an MA in International Relations, both from the University of Warwick, and also studied for one academic year at the University of Salzburg in Austria. Full Article
ad Queen Elizabeth II Academy for Leadership Announces 2018/19 Fellows By feedproxy.google.com Published On :: Mon, 24 Sep 2018 08:16:49 +0000 1 October 2018 The Queen Elizabeth II Academy for Leadership in International Affairs, based at Chatham House, is delighted to announce the arrival of its new cohort of Academy fellows. 2018-10-01-CH.jpg The Academy was launched by Her Majesty the Queen in November 2014 to offer potential and established leaders from around the world the opportunity to spend ten months as Academy fellows and develop the tools needed to address the major policy challenges and critical issues facing the world today.Academy fellows are drawn from government and the broader policy community, the private sector, media and civil society. During their time at the Academy, fellows deepen their understanding of critical issues, learn new skills, develop their networks and propose new ideas and solutions to complex policy challenges and opportunities.Dr Leslie Vinjamuri, Dean, QEII Academy for Leadership in International Affairs says:'Chatham House recognizes the need for inspirational and effective leadership in today’s complex and rapidly changing global environment. We remain absolutely committed to the mission of developing leadership skills and feel privileged to welcome the 2018-19 Academy Fellows. The Queen Elizabeth II Academy is uniquely well-positioned, drawing on the historical depth of expertise at Chatham House, our international and national networks, and the dynamism of London to develop skills, knowledge, and global insights that benefit emerging and accomplished leaders across diverse sectors in Europe, Africa, the Middle East, Asia and the Americas.'Academy Fellows 2018/19Rustam AnshbaRustam’s research will explore the prospects for transforming the Georgian-Abkhaz conflict. He will be hosted by the Russia and Eurasia Programme. His fellowship is supported by the Robert Bosch Stiftung.Rita DayoubRita will analyse attacks against healthcare systems during conflicts in Syria and South Sudan. She will be hosted by the Centre on Global Health Security. Her fellowship is supported by the Asfari Foundation.Isabel DunstanIsabel’s research will focus on digital literacy among women as a means to counter radicalization and intolerance in Indonesia. She will be hosted by the Asia-Pacific Programme. Her fellowship is supported by Mr Richard Hayden.Sophia IgnatidouSophia will examine the political and security implications of Artificial Intelligence. She will be hosted by the International Security Department. Her fellowship is supported by the Stavros Niarchos Foundation.Anna KorbutAnna’s research will examine the current media landscape in Ukraine and its transformative potential. She will be hosted by the Russia and Eurasia Programme. Her fellowship is supported by the Robert Bosch Stiftung.Damir KurtagicDamir will research the challenges and possibilities of private sector engagement in Sub-Saharan Africa. He will be hosted by the Africa Programme. His fellowship is supported by the Robert Bosch Stiftung.Zaki MehchyZaki will research the role and dynamics of non-state actors in Syria and their relationship with state institutions. He will be hosted by the Middle East and North Africa Programme. His fellowship is supported by the Asfari Foundation.Anne NyambaneAnne will examine the synergies and trade-offs involved in the implementation of the Sustainable Development Goals (SDGs). She will be hosted by the Energy, Environment and Resources Department. Her fellowship is supported by the Mo Ibrahim Foundation.MasterclassThe Academy is also pleased to welcome three Masterclass participants from the European Bank for Reconstruction and Development. Full Article
ad Chatham House appoints Rob Yates as the new head of the Centre on Global Health Security By feedproxy.google.com Published On :: Thu, 27 Jun 2019 09:35:01 +0000 27 June 2019 Chatham House is pleased to announce that Rob Yates has been appointed as head of the Centre on Global Health Security. Yates.jpg He brings decades of experience as a health economist working in international development and health and is an internationally recognized expert on universal health coverage (UHC) and progressive health financing, operating at the highest political levels.For the past five years, Rob has led the Centre’s work on Universal Health Coverage (UHC) as director of its UHC Policy Forum, which works on the political economy of UHC reform processes and advises political leaders and government ministries on how to plan, finance and implement national UHC reforms.He has also worked closely with The Elders on presenting policy options on universal health reforms to heads of state across the world. Before leading the UHC Policy Forum at Chatham House, Rob was a senior health economist at the World Health Organization from 2011 to 2014, after moving from the UK Department for International Development (DFID), where he was a senior health economist. Prior to that, Rob was the deputy head of the Integrated UN Office in the Democratic Republic of Congo. He also spent five years working for the government of Uganda as a senior health economist, on secondment from DFID during the early 2000s.'I am delighted to welcome Rob Yates as the head of the Centre on Global Health Security. He will bring a wealth of experience to the role at a time of risk but also great opportunity in the sector,' said Dr Robin Niblett, director of Chatham House. 'Rob will continue to work on his own area of expertise – universal health coverage – while ensuring the Centre continues to address other major global health challenges that manifest themselves as foreign policy and international affairs problems.'Rob replaces David Heymann, who retires from the role as the Centre marks its 10th anniversary but will remain involved in several of the Centre’s projects.'I would also like to pay tribute to David Heymann, who launched the Centre on Global Health Security in 2009 to examine key global health challenges in international affairs and world politics,' Niblett added. 'Without David the Centre would not have had the impact that it has and I am truly grateful for his hard work and achievements over the last 10 years.'Yates takes up his post this week.'I am honoured to become the new head of the Centre on Global Health Security and build on the successes delivered by David Heymann and the team over the last decade,' he said. 'My priority as the new head will be to ensure that our research and activities have a real impact in accelerating progress towards the Sustainable Development Goals by focusing on improving health security and health coverage in countries across the world. Engaging in issues related to the political economy of health and health care reforms will be critical in achieving this impact.' Full Article
ad Creon Butler appointed to lead Global Economy and Finance Programme By feedproxy.google.com Published On :: Tue, 22 Oct 2019 10:22:32 +0000 22 October 2019 Creon Butler has been appointed to lead the Global Economy and Finance programme at Chatham House, joining the institute at the beginning of December. He will also form part of the institute’s senior leadership team. Creon will join Chatham House from the Cabinet Office where he served as director for international economic affairs in the National Security Secretariat and G7/G20 ‘sous sherpa’, advising on global policy issues such as climate change, natural resource security, global health threats and the future of the international economic architecture.Creon first joined the Cabinet Office in 2013 as director in the European and Global Issues Secretariat, advising prime minister David Cameron on international economic and financial issues, ranging from country-specific developments in China and Germany to global challenges such as antimicrobial resistance and anticorruption. He designed and organized the UK’s global Anti-Corruption Summit in May 2016. Earlier in his career, he served in the Bank of England, HM Treasury and in the Foreign and Commonwealth Office, where he was director for economic policy and chief economic adviser. He was also deputy high commissioner in New Delhi from 2006 to 2009.Robin Niblett, director of Chatham House, said: 'We are delighted that Creon Butler will join Chatham House at such an important moment, when geoeconomic competition and technological disruption are changing the structure of the global economy, and as governments and societies across the world must develop more sustainable pathways to economic growth. Creon brings precisely the right combination of knowledge and experience to enable Chatham House to conceive inclusive solutions for the future.'Creon Butler said: “Chatham House’s high quality, independent and focused policy research has never been more important in helping policy makers to chart the best path given today’s extraordinary economic and political uncertainties. I am very pleased to have the opportunity to lead the institute’s Global Economy and Finance programme at this critical time.' Full Article
ad Sir David Attenborough and the BBC Studios Natural History Unit awarded Chatham House Prize 2019 for ocean advocacy By feedproxy.google.com Published On :: Mon, 18 Nov 2019 13:13:54 +0000 19 November 2019 The 2019 Chatham House Prize is awarded to Sir David Attenborough and Julian Hector, head of BBC Studios Natural History Unit, for the galvanizing impact of the Blue Planet II series on tackling ocean plastic pollution. 2019-06-06-DavidAttenboroughB.jpg The Chatham House Prize is awarded to the person, persons or organization who is deemed to have made the most significant contribution to the improvement of international relations in the previous year. The presentation ceremony and panel discussion with the winners will be livestreamed on Wednesday.The Blue Planet II series highlighted the damage caused by discarded plastics to the world’s oceans and marine wildlife. It is estimated that there are more than 150 million tonnes of plastic in the world’s oceans; resulting in the deaths of 1 million birds and 100,000 sea mammals each year. Dr Robin Niblett, director of Chatham House said: ‘Plastic pollution is one of the gravest challenges facing the world’s oceans, and undoubtedly an international issue. Sir David and the BBC Studios Natural History Unit played an instrumental role in helping to put this issue at the forefront of the public agenda. Blue Planet II spurred a passionate global response and generated clear behavioural and policy change.’This year the G20 agreed on an international framework to address marine plastic litter, acknowledging the increasing urgency of the issue and the need for an international solution. This follows action from the UK government, including a plan to ban common plastic items and investment in global research.See full award citationRead more about Chatham House's research work in this areaOther nomineesDr Niblett thanked Chatham House members for voting and acknowledged the outstanding achievements of the 2019 nominees:Abiy Ahmed, prime minister of Ethiopia, nominated for his efforts to transform civic leadership and promote plural politics, free speech and peace in Ethiopia Katrín Jakobsdóttir, prime minister of Iceland, nominated for her commitment to gender equality and women’s financial inclusion in Iceland EventThe Prize was presented to Sir David and Julian Hector by Her Majesty The Queen at Chatham House on Wednesday 20 November.Watch video from the eventFor more information please contactChatham House Press Officepressoffice@chathamhouse.org+44 (0)207 957 5739BBC Studios Natural History Unit Communications ManagerLynn.li@bbc.co.uk+44 (0) 7513 137893About the Chatham House PrizeThe Chatham House Prize is voted for by Chatham House members, following nominations from the institute’s staff. The award is presented on behalf of the institute's patron, Her Majesty the Queen, representing the non-partisan and authoritative character of the Prize.The Chatham House Prize was launched in 2005. Previous recipients of the Prize include the Committee to Protect Journalists, Colombian president Juan Manuel Santos, president of Ghana John Kufuor, Médecins Sans Frontières and Melinda Gates, co-founder of the Bill and Melinda Gates Foundation.Chatham House is a world-leading policy institute based in London. Our mission is to help governments and societies build a sustainably secure, prosperous and just world. We engage governments, the private sector, civil society and our members in open debate and private discussions about the most significant developments in international affairs. Our research and policy ideas involve rigorous analysis of critical global, regional and country-specific challenges and opportunities.About BBC Studios Natural History Unit BBC Studios Natural History Unit produces the world’s most iconic natural history programmes, such as Blue Planet II and Planet Earth II, which have been watched by more than a billion people globally. Ranging from technically challenging live shows and super-landmarks to long-running series and children’s content, The Natural History Unit programmes include Dynasties, Blue Planet Live, Springwatch, Animal Babies: First Year On Earth, Andy’s Dinosaur Adventures as well as the currently on air Seven Worlds, One Planet presented by Sir David Attenborough and third-party commissions for Discovery, Apple, Quibi, National Geographic and BBC America. The Natural History Unit is part of BBC Studios, a subsidiary of the BBC, which develops, produces and distributes bold, British content, making over 2,500 hours of content each year, operating in 22 markets globally and generating revenue of around £1.4bn. In the year to March 2019, it returned £243m to the BBC Group, complementing the BBC’s licence fee and enhancing programmes for UK audiences. Related pages Managing Natural Resources Energy, Environment and Resources Programme Full Article
ad Transatlantic Strategy Group on the Future of US Global Leadership: Responding to a Revanchist Russia By feedproxy.google.com Published On :: Mon, 08 Sep 2014 13:30:01 +0000 Invitation Only Research Event 12 September 2014 - 8:45am to 5:00pm Chatham House, London Meeting Notepdf | 129.55 KB The situation in Ukraine remains in flux and despite Europe and the US toughening sanctions on Russia, President Putin continues to increase the scope of Russia’s involvement in the conflict between the Ukrainian government and the separatists. It remains unclear how far Putin is willing to go, what his broader regional ambitions are, and what he will do if forced further into a corner by Western actions. In this time of uncertainty and instability it is therefore vital to assess how the transatlantic partners should respond to this increasingly precarious situation. At this all-day event, the group will discuss how US policy towards Russia is changing, what this means for Europe and, subsequently, how Europe should respond. Attencance at this event is by invitation only.The event is part of the Transatlantic Strategy Group on the Future of US Global Leadership run jointly with the German Marshall Fund of the United States. Over the course of a year, this group will come together to discuss how US policy is changing on key issues and the implications for Europe. This project is supported by the Fritz Thyssen Stiftung. Department/project US and the Americas Programme Rory Kinane +44 (0) 20 7314 3650 Email Full Article
ad Advancing the 2014 NATO Summit Deliverables By feedproxy.google.com Published On :: Fri, 17 Oct 2014 14:45:02 +0000 Invitation Only Research Event 30 October 2014 - 1:15pm to 31 October 2014 - 5:00pm Chatham House, London Meeting Summarypdf | 88.25 KB Event participants Xenia Wickett, Project Director, US; Dean, Academy for Leadership in International Affairs, Chatham HouseDr Christian Moelling, International Security Division Associate, SWP-Berlin The NATO Summit, held in September in Newport, Wales, was a way point in the larger strategic vision for NATO over the coming decade. The deliverables that the leaders laid out must now been acted upon. NATO and its member states must find ways to more effectively harness their significant resources to meet the challenges ahead, from the ongoing conflicts in Ukraine and the Middle East, to the longer term threats posed by cyber-attack and energy insecurity.The event will bring together senior representatives from a number of the NATO member states, NATO partners and external experts from industry, the media and the think-tank and academic communities, to discuss how best to move the deliverables forward, and how to most effectively work together in so doing.This is the first of two workshops being held in collaboration with SWP-Berlin. Department/project NATO: Charting the Way Forward Richard Gowing Programme Administrator +44 (0)20 7389 3270 Email Full Article
ad Transatlantic Strategy Group on the Future of US Global Leadership: Transatlantic Security Policy Towards a Changing Middle East By feedproxy.google.com Published On :: Thu, 05 Mar 2015 11:45:02 +0000 Invitation Only Research Event 6 February 2015 - 8:45am to 4:30pm Residence of the British Ambassador to France, Paris Meeting Summarypdf | 95.65 KB With the Middle East in chaos and the future of many states increasingly uncertain, there is a large amount of attention as to how policy-makers in Europe and the US should respond. In particular, many in Europe are unsure of long-term US policy in light of competing American priorities, budgetary constraints and a public adverse to committing further resources abroad. In this context, it is important that European and American policy-makers understand each other’s positions.At this all-day event, a group of experts will discuss how US policy towards the Middle East is changing, what this means for Europe and, subsequently, how Europe should respond. Attendance at this event is by invitation only.The workshop is held as part of the Transatlantic Strategy Group on the Future of US Global Leadership run jointly with the German Marshall Fund of the United States. Over the course of a year, this group will discuss how US policy is changing on key issues and the implications for Europe. This project is supported by the Fritz Thyssen Foundation, with support for this event provided by the Delegation of Strategic Affairs of the French Ministry of Defence and the British Embassy in Paris. Event attributes External event Department/project US and the Americas Programme Full Article
ad Transatlantic Strategy Group on the Future of US Global Leadership: Global Institutions and the Economy of the Future By feedproxy.google.com Published On :: Thu, 01 Oct 2015 13:30:01 +0000 Invitation Only Research Event 10 June 2015 - 8:45am to 4:30pm Bertelsmann Foundation, Berlin, Germany Meeting Summarypdf | 154.74 KB Europe and the United States have dominated global institutions for over 70 years. However, as the emerging markets take up a greater share of the global economy it is becoming increasingly difficult for the transatlantic powers to maintain the current system. This event will examine the changes needed in order to avoid a collapse of the current system.The workshop is held as part of the Transatlantic Strategy Group on the Future of US Global Leadership run jointly with the German Marshall Fund of the United States. Over the course of a year, this group will discuss how US policy is changing on key issues and the implications for Europe. This project is supported by the Fritz Thyssen Foundation, with support for this event provided by the Bertelsmann Foundation. Event attributes External event Department/project US and the Americas Programme US and Americas Programme Email Full Article
ad The Future of US Global Leadership: Implications for Europe, Canada and Transatlantic Cooperation By feedproxy.google.com Published On :: Thu, 05 May 2016 09:13:42 +0000 10 May 2016 As the United States’ international engagement changes, Canada and Europe should increase coordination with it to prevent power vacuums from emerging. Download PDF Xenia Wickett Former Head, US and the Americas Programme; Former Dean, The Queen Elizabeth II Academy for Leadership in International Affairs @xeniawickett LinkedIn Rory Kinane Former Manager, US and the Americas Programme 2016-05-06-future-us-global-leadership.jpg Marine One, carrying US President Barack Obama, departs the White House on 26 August 2014, Washington DC. Photo: Getty Images. SummaryThe United States’ transatlantic allies need to appreciate how its global leadership is changing and what this means for their interests, and respond accordingly. Notions of US decline have been overstated, but the country is not going to play the same international role in the future that it has previously.As the United States’ international engagement changes, Canada and Europe should increase coordination with it to prevent power vacuums from emerging. The transatlantic allies should work together to build greater links at all stages of the policy process, from perceptions of threat, prioritization, analysis, threat definition and policy formation to implementation and action. As the United States’ capabilities adapt to its changed circumstances and role, so too must those of its allies. This adjustment must go far beyond military aspects to enhancing diplomatic, energy, economic, intelligence and other resources.In addition to the challenges around differing interests, priorities and capabilities inherent in any alliance, Europe appears to have lost its confidence. In part this is due to its growing disengagement and introspection. But Europe retains huge potential for influence if it uses its resources effectively. There is much that European states can do, individually and together, to take more control over advancing their strategic interests. Equally, by working together they can do much to nudge the United States in helpful directions to support the mutual interests of all parties.The conversation on reforming global institutions such as the IMF must move beyond the need for change per se towards articulating the actual shape of such changes. Europe and Canada will likely need to push the United States into accepting reform of these institutions to better reflect today’s reality and tomorrow’s challenges. Global institutions need more diversified leaderships if they are to ensure their long-term legitimacy and influence. This will be difficult to push through politically in the United States, but by working with new regional and global powers to propose reforms, Europe and Canada can help find an acceptable solution.The use of ad hoc coalitions does not necessarily damage the efficacy of broader consensus institutions such as NATO. In fact, flexible coalitions may often be desirable when solutions to new challenges need to be developed and agreed quickly.Canada and Europe should consider partnering with other actors besides the United States where necessary. This may be expedient for meeting individual objectives, and would have the secondary benefit of demonstrating to emerging powers that the West does not exclude cooperation with others out of an arbitrary loyalty to the United States.Europe needs to appreciate the potentially dire consequences of failing to adapt to changing US leadership and an increasingly complex world. There is a real chance that the European project could unravel in the next few years due to external and internal pressures. While many European policy-makers display an understanding of these challenges in private, in public there is little appetite for taking the decisions necessary to bring long-term stability to the continent. Department/project US and the Americas Programme Full Article
ad For a US Trade Deal, UK Should Secure Its Spot in TTIP After Brexit By feedproxy.google.com Published On :: Thu, 25 Aug 2016 13:39:08 +0000 25 August 2016 Marianne Schneider-Petsinger Senior Research Fellow, US and the Americas Programme @mpetsinger Having Britain as an additional party to a US−EU free-trade agreement would benefit all sides. 2016-08-25-UnionNY.jpg A Union flag hangs in the window of a British grocery store in New York City. Photo by Getty Images. Even though President Barack Obama cautioned that the UK would be at the ‘back of the queue’ for a trade agreement with the US if the country chose to leave the EU, in the post-Brexit world a deal might be struck more swiftly. Various ideas for bringing the UK and US into a formal trade arrangement have been floated – ranging from a bilateral UK-US trade deal, or the UK joining NAFTA (the North American Free Trade Agreement between the US, Canada and Mexico), to the UK becoming a part of the TPP (the Trans-Pacific Partnership that the US is pursuing with 11 other countries along the Pacific Rim). However, one option stands out: opening the Transatlantic Trade and Investment Partnership (TTIP), which the US and EU are currently negotiating, to the UK after Brexit.Good reasons for Britain in TTIPFirst, from the perspective of the UK, signing up to TTIP would mean a more comprehensive deal with the US than a bilateral UK−US trade agreement. For instance, Britain is very keen to include financial services regulation in any trade agreement with America, but given Washington’s reluctance, this ambition might only be achievable if other countries like France and Germany throw their financial weight into the negotiations.Second, continuing involvement in the TTIP negotiations allows London to begin securing its trade position with the US now. Though its influence in the EU may weaken as it heads for the exit, Britain could make the best use of influencing the EU position on TTIP while it is still a member. It could then accept the terms of TTIP and accede as a third party relatively quickly after exiting the EU. Official negotiations on a UK−US-only deal would have to wait until the UK has left the EU, as trade talks fall under the exclusive competence of the EU.Third, for the US and EU, having the UK as a party to TTIP would ensure the scale of the deal is not reduced, and thereby maintain the strategic appeal and ability to set global standards. At the moment, the UK is the EU’s second-largest economy, accounting for approximately 18 per cent of GDP. With Britain in TTIP, the sheer size of the transatlantic market space will have more pull for other countries to adopt the common transatlantic rules in order to gain market access.Fourth, the UK joining TTIP as a third party would establish the agreement as an ‘open platform’ that is available for other countries to join. Michael Froman, the United States trade representative, has characterized TTIP as being such an open agreement. EU representatives have been more ambivalent, though this is starting to change in the wake of Brexit. David O’Sullivan, the current EU ambassador to the US, recently said that as ‘we’ve always seen TTIP as a potential open platform, [the] UK could still benefit [from it] even not as a member of the European Union’. While now might not be the right time to expand the TTIP bloc beyond its original participants given that negotiations are already complex and drawn out, it would be beneficial for the negotiating partners to send a strong message that countries that are willing and able to commit to the high TTIP standards will be welcomed later on.Obstacles to Britain in TTIPBut before the UK could be added to TTIP after Brexit, major hurdles will have to be jumped and crucial questions answered. The first obstacle is actually getting a TTIP deal, which will require significant efforts by political leaders and negotiators on both sides of the Atlantic.Second, selling the ‘UK in TTIP option’ to Brexiteers will not be an easy task. After all, Leave campaigners argued that the US−EU deal might undermine the NHS and was thus presented as one of the reasons to cut loose from Brussels. As the major rationale behind TTIP is regulatory harmonization, if the UK were to sign up to TTIP it would still have to apply many EU rules. This, however, would go counter to the arguments for leaving the EU in the first place.Third, it will be a challenging job for the UK to untangle its trade relationship with the EU while at the same time negotiating TTIP together with the EU. It would be easiest if the UK decided to remain a member of the EU customs union. Britain would then be required to impose the EU’s external tariffs on countries like the US. This would fit seamlessly with the ‘UK in TTIP’ option. But as the UK will most likely pull out of the customs union, it will be more complicated than that.Finally, the timing of Brexit and the TTIP negotiations could cause complications. In the unlikely event that a US-EU free trade deal is concluded and ratified while the UK is still a member of the EU, the agreement (or the parts of it that fall under national competence) would most likely continue to apply to Britain after Brexit without the need for accession. If the TTIP negotiations continue beyond Brexit, then the UK would move from negotiating as part of the EU bloc to becoming a third party. This raises the issue of whether the UK and EU continue to negotiate as one bloc vis-à-vis the US.Special economic relationshipStill, the depth of the economic ties between the US and UK means that the TTIP option is likely to be welcomed favourably by both countries. The US is the most important single export market for the UK, with goods and services worth £45 billion shipped in 2015. Last year, the US ranked third (after Germany and China) as a source for UK imports. With nearly $1 trillion invested in each other’s economies, the US and the UK are also each other’s largest investors. Given this special economic relationship, Britain is unlikely to be at the ‘back of the queue’ in any event. But the TTIP option is the best path to preserving and strengthening the relationship post-Brexit while also realizing the wider strategic benefits of a transatlantic trade agreement.A version of this article appeared on Real Clear World.To comment on this article, please contact Chatham House Feedback Full Article
ad Beneath the Bluster, Trump Offers the Chance to Rethink Trade By feedproxy.google.com Published On :: Mon, 12 Dec 2016 14:58:53 +0000 12 December 2016 Marianne Schneider-Petsinger Senior Research Fellow, US and the Americas Programme @mpetsinger Trump’s trade policy may not be as radical in practice as he described it on the stump, and his win is an opportunity to address the shortcomings in the current global trade system. 2016-12-12-TrumpTrade.jpg Trump has pointed to some valid concerns about the current trading system. Photo by Getty Images. With Donald Trump in the White House, US trade policy will probably look very different from the past 70 years - seven decades across which successive Republican and Democratic administrations have participated in and led global trade liberalization initiatives. If the president-elect delivers on his major campaign promises on trade, the negative effects on the American economy would be severe and the United States would give up its role in shaping the global trading system.But there is no need to panic. Trump will likely leave behind the rhetoric of the campaign trail once he sits in the Oval Office. Trump will probably moderate his proposals, because a faction of the Republican-dominated Congress continues to support free trade. He might also be reined in by his team, though that depends on who best catches the ear of the president: individuals such as Vice-President-elect Mike Pence, who has supported free-trade agreements in the past, or trade-skeptical advisors such as Dan DiMicco, who now heads the transition team for the Office of the United States Trade Representative. So what does the Trump presidency actually mean for trade?Trump won’t likely follow through on his most extreme plans, such as leaving the World Trade Organization. But he will lead a more protectionist United States that focuses on its trade deficits – with particular attention being paid to China and Mexico. Trump will probably impose tariffs on imports from those countries; however, duties will be lower than the mooted 45 per cent and 35 per cent, respectively. With regards to China, Trump will probably bring trade cases against Beijing’s subsidy arrangements and look into alleged currency manipulation (even though most economists accept that the renminbi is no longer undervalued).Given the prominence of the North American Free Trade Agreement on the campaign trail, Trump will have to address the deal with Canada and Mexico. Whether that means renegotiating or pulling out remains to be seen. One thing is certain: Trump will not move forward with mega-regional trade accords such as the Trans-Pacific Partnership or the US-EU Transatlantic Trade and Investment Partnership. Those would-be pacts are a lost opportunity, but this is not the end of the trade world. Trump will focus instead on striking trade deals with individual countries. One such potential bilateral trade deal could be a US–UK agreement, which Trump and his advisers, despite the prognostications of the current president, see at the front of the queue. Opportunity to rethink the trade frameworkThe fact that Trump is not necessarily against free trade per se bears hope. And there is another silver lining in the dark cloud hanging over trade. Trump has pointed to some valid concerns about the current trading system. His victory can be an opportunity to address these shortcomings. NAFTA does need an update. The agreement entered into force in 1994 - before the internet took off. Thus, provisions to include standards to protect digital freedoms could modernize NAFTA and expand its scope to cover 21st century economic issues. In addition, labour rights and environmental protections were not included in NAFTA but were incorporated into side agreements with weak, unenforceable provisions. By better addressing labour and environmental issues, NAFTA could be significantly upgraded.Trump will aim to tackle unfair competition and look to enforce existing trade deals more vigilantly. This is another important and legitimate issue, and could be tackled in conjunction with European allies. The European Commission has recently proposed redesigning and updating its trade defence instruments because non-market economy practices and state intervention by some WTO countries - for example, China’s overcapacity in the steel sector - have hurt domestic industries. Without action by major players such as the United States or the European Union, China would have no incentive to reform its distortionary policies. Trust in the rules-based trading system requires that existing trade agreements are properly and fairly enforced.Trump’s win highlights the need for better compensation for those who have felt the adverse effects of trade. His victory was partly fuelled by tapping into economic anxieties and appealing to voters who feel left behind by globalization. Better mechanisms to cushion the blows to the losers of globalization are indeed required. In the United States, Trade Adjustment Assistance has been insufficiently funded and is ineffective. More needs to be done to replace the wages of workers whose jobs have been lost due to trade and to provide them with skills training for re-employment. This reconsideration of assistance for those who are hurt by free trade could provide a foundation for the future. Once the current wave of anti-trade sentiment subsides, new trade agreements can be struck that don’t leave so many citizens feeling left behind. Instead of worrying about how Trump might blow up the underpinnings of the global trading system, this is an opportunity to rethink what a new trade framework might look like.This piece was published in collaboration with Real Clear World.To comment on this article, please contact Chatham House Feedback Full Article
ad Up in smoke? Global tobacco advocacy and local mobilization in Africa By feedproxy.google.com Published On :: Wed, 04 Sep 2019 14:05:11 +0000 4 September 2019 , Volume 95, Number 5 Amy S. Patterson and Elizabeth Gill Read online Even though most African states have signed and ratified the Framework Convention on Tobacco Control (FCTC), a global treaty to limit tobacco use, African states have been slow to pass and implement tobacco control policies like regulations on sales, smoke-free environments and taxes. This article examines how the ineffectiveness of local tobacco-control advocacy contributes to this suboptimal outcome. It asserts that the disconnect between the global tobacco-control advocacy network and local advocates shapes this ineffectiveness. With funding and direction predominately from the Bloomberg Initiative, local advocates emulate the funders' goal of achieving quick, measurable policy results. Their reliance on the network drives African advocates to strive to pass legislation, even in difficult political climates, and to remake their agendas when funders change their priorities. They also emulate the network's focus on evidence-based arguments that stress epidemiological data and biomedical interventions, even when this issue frame does not resonate with policy-makers. Financial dependence can draw local advocates into expectations about patronage politics, undermine their ability to make principled arguments, and lead them to downplay the ways that their home country's socioeconomic and cultural contexts affect tobacco use and control. Based on key informant interviews with African advocates, media analysis and the case-studies of Ghana and Tanzania, the article broadens the study of philanthropy in global health, it adds an African perspective to the literature on global health advocacy, and it deepens knowledge on power dynamics between external funders and local actors in the realms of health and development. Full Article
ad The NHS Is Not for Sale – But a US–UK Trade Deal Could Still Have an Impact By feedproxy.google.com Published On :: Fri, 29 Nov 2019 15:53:59 +0000 29 November 2019 Dr Charles Clift Senior Consulting Fellow, Global Health Programme @CliftWorks Charles Clift examines what recently leaked documents mean – and do not mean – for healthcare in transatlantic trade negotiations. 2019-11-29-NHS.jpg Kings College Hospital in London. Photo: Getty Images. The leaked record of the five meetings of the UK–US Trade & Investment Working Group held in 2017–18 has led to a controversy in the UK election campaign around the claim that ‘the NHS is up for sale’.But a careful reading of the leaked documents reveals how remarkably little concerns the NHS – in five meetings over 16 months, the NHS is mentioned just four times. The patent regime and how it affects medicines is discussed in more depth but largely in terms of the participants trying to understand each other’s systems and perspectives. For the most part, the discussions were overwhelmingly about everything else a trade deal would cover other than healthcare – matters such as subsidies, rules of origin and customs facilitation.But this does not mean there will be no impact on Britain’s health service. There are three main concerns about the possible implications of a US–UK trade deal after Brexit – a negotiation that will of course only take place if the UK remains outside the EU customs union and single market and also does not reach a trade agreement with the EU that proves incompatible with US negotiating objectives.One concern is that the US aim of securing ‘full market access for US products’, expressed in the US negotiating objectives, will affect the ability of NICE (The National Institute for Health and Care Excellence) to prevent the NHS from procuring products that are deemed too expensive in relation to their benefits. It could also affect the ability of the NHS to negotiate with companies to secure price reductions as, for instance, happened recently with Orkambi, a cystic fibrosis drug.A peculiarity of the main US government healthcare programme (Medicare) is that it has historically not negotiated drug prices, although there are several bills now before Congress aiming to change that. US refusal to negotiate or control prices is one reason that US drug prices are the highest in the world. A second concern is that the US objective of securing ‘intellectual property rights that reflect a standard of protection similar to that found in US law’ will result in longer patent terms and other forms of exclusivity that will increase the prices the NHS will have to pay for drugs.However, it is not immediately apparent that UK standards are significantly different from those in the US – the institutional arrangements differ but the levels of protection offered are broadly comparable. Recent publicity about a potential extra NHS medicine bill of £27 billion resulting from a trade deal is based on the NHS having to pay US prices on all drugs – which seems an unlikely outcome unless the UK contingent are extraordinarily bad negotiators.Nevertheless, in an analysis section (marked for internal distribution only), the UK lead negotiator noted: ‘The impact of some patent issues raised on NHS access to generic drugs (i.e. cheaper drugs) will be a key consideration going forward.’A third concern is that the US objective of providing ‘fair and open conditions for services trade’ and other US negotiating objectives will oblige the UK to open up the NHS to American healthcare companies.This is where it gets complicated. At one point in a discussion on state-owned enterprises (SOEs) the US asked if the UK had concerns about their ‘health insurance system’ (presumably a reference to the NHS). The UK response was that it ‘wouldn’t want to discuss particular health care entities at this time, you’ll be aware of certain statements saying we need to protect our needs; this would be something to discuss further down the line…’On this exchange the UK lead negotiator commented: ‘We do not currently believe the US has a major offensive interest in this space – not through the SOE chapter at least. Our response dealt with this for now, but we will need to be able to go into more detail about the functioning of the NHS and our views on whether or not it is engaged in commercial activities…’On the face of it, these documents provide no basis for saying the NHS would be for sale – whatever that means exactly. The talks were simply an exploratory investigation between officials on both sides in advance of possible negotiations.But it is a fact that US positions in free trade agreements are heavily influenced by corporate interests. Their participation in framing agreements is institutionalized in the US system and the pharmaceutical and healthcare industries in the US spend, by a large margin, more on lobbying the government than any other sector does. Moreover, President Donald Trump has long complained about ‘the global freeloading that forces American consumers to subsidize lower prices in foreign countries through higher prices in our country’.It is when (and if) the actual negotiations on a trade deal get under way that the real test will come as the political profile and temperature is raised on both sides of the Atlantic. Full Article
ad Cohomologie ????-adique de la tour de Drinfeld: le cas de la dimension 1 By www.ams.org Published On :: Tue, 10 Mar 2020 10:59 EDT Pierre Colmez, Gabriel Dospinescu and Wiesława Nizioł J. Amer. Math. Soc. 33 (2019), 311-362. Abstract, references and article information Full Article
ad Large Scale Screening for Novel Rab Effectors Reveals Unexpected Broad Rab Binding Specificity By feedproxy.google.com Published On :: 2008-06-01 Mitsunori FukudaJun 1, 2008; 7:1031-1042Research Full Article
ad A Proteome-wide, Quantitative Survey of In Vivo Ubiquitylation Sites Reveals Widespread Regulatory Roles By feedproxy.google.com Published On :: 2011-10-01 Sebastian A. WagnerOct 1, 2011; 10:M111.013284-M111.013284Research Full Article
ad Discordant Protein and mRNA Expression in Lung Adenocarcinomas By feedproxy.google.com Published On :: 2002-04-01 Guoan ChenApr 1, 2002; 1:304-313Research Full Article
ad The hibernating 100S complex is a target of ribosome-recycling factor and elongation factor G in Staphylococcus aureus [Protein Synthesis and Degradation] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The formation of translationally inactive 70S dimers (called 100S ribosomes) by hibernation-promoting factor is a widespread survival strategy among bacteria. Ribosome dimerization is thought to be reversible, with the dissociation of the 100S complexes enabling ribosome recycling for participation in new rounds of translation. The precise pathway of 100S ribosome recycling has been unclear. We previously found that the heat-shock GTPase HflX in the human pathogen Staphylococcus aureus is a minor disassembly factor. Cells lacking hflX do not accumulate 100S ribosomes unless they are subjected to heat exposure, suggesting the existence of an alternative pathway during nonstressed conditions. Here, we provide biochemical and genetic evidence that two essential translation factors, ribosome-recycling factor (RRF) and GTPase elongation factor G (EF-G), synergistically split 100S ribosomes in a GTP-dependent but tRNA translocation-independent manner. We found that although HflX and the RRF/EF-G pair are functionally interchangeable, HflX is expressed at low levels and is dispensable under normal growth conditions. The bacterial RRF/EF-G pair was previously known to target only the post-termination 70S complexes; our results reveal a new role in the reversal of ribosome hibernation that is intimately linked to bacterial pathogenesis, persister formation, stress responses, and ribosome integrity. Full Article
ad The cytochrome P450 enzyme CYP24A1 increases proliferation of mutant KRAS-dependent lung adenocarcinoma independent of its catalytic activity [Cell Biology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 We previously reported that overexpression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) increases lung cancer cell proliferation by activating RAS signaling and that CYP24A1 knockdown inhibits tumor growth. However, the mechanism of CYP24A1-mediated cancer cell proliferation remains unclear. Here, we conducted cell synchronization and biochemical experiments in lung adenocarcinoma cells, revealing a link between CYP24A1 and anaphase-promoting complex (APC), a key cell cycle regulator. We demonstrate that CYP24A1 expression is cell cycle–dependent; it was higher in the G2-M phase and diminished upon G1 entry. CYP24A1 has a functional destruction box (D-box) motif that allows binding with two APC adaptors, CDC20-homologue 1 (CDH1) and cell division cycle 20 (CDC20). Unlike other APC substrates, however, CYP24A1 acted as a pseudo-substrate, inhibiting CDH1 activity and promoting mitotic progression. Conversely, overexpression of a CYP24A1 D-box mutant compromised CDH1 binding, allowing CDH1 hyperactivation, thereby hastening degradation of its substrates cyclin B1 and CDC20, and accumulation of the CDC20 substrate p21, prolonging mitotic exit. These activities also occurred with a CYP24A1 isoform 2 lacking the catalytic cysteine (Cys-462), suggesting that CYP24A1's oncogenic potential is independent of its catalytic activity. CYP24A1 degradation reduced clonogenic survival of mutant KRAS-driven lung cancer cells, and calcitriol treatment increased CYP24A1 levels and tumor burden in Lsl-KRASG12D mice. These results disclose a catalytic activity-independent growth-promoting role of CYP24A1 in mutant KRAS-driven lung cancer. This suggests that CYP24A1 could be therapeutically targeted in lung cancers in which its expression is high. Full Article
ad SUMOylation of the transcription factor ZFHX3 at Lys-2806 requires SAE1, UBC9, and PIAS2 and enhances its stability and function in cell proliferation [Protein Synthesis and Degradation] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 SUMOylation is a posttranslational modification (PTM) at a lysine residue and is crucial for the proper functions of many proteins, particularly of transcription factors, in various biological processes. Zinc finger homeobox 3 (ZFHX3), also known as AT motif-binding factor 1 (ATBF1), is a large transcription factor that is active in multiple pathological processes, including atrial fibrillation and carcinogenesis, and in circadian regulation and development. We have previously demonstrated that ZFHX3 is SUMOylated at three or more lysine residues. Here, we investigated which enzymes regulate ZFHX3 SUMOylation and whether SUMOylation modulates ZFHX3 stability and function. We found that SUMO1, SUMO2, and SUMO3 each are conjugated to ZFHX3. Multiple lysine residues in ZFHX3 were SUMOylated, but Lys-2806 was the major SUMOylation site, and we also found that it is highly conserved among ZFHX3 orthologs from different animal species. Using molecular analyses, we identified the enzymes that mediate ZFHX3 SUMOylation; these included SUMO1-activating enzyme subunit 1 (SAE1), an E1-activating enzyme; SUMO-conjugating enzyme UBC9 (UBC9), an E2-conjugating enzyme; and protein inhibitor of activated STAT2 (PIAS2), an E3 ligase. Multiple analyses established that both SUMO-specific peptidase 1 (SENP1) and SENP2 deSUMOylate ZFHX3. SUMOylation at Lys-2806 enhanced ZFHX3 stability by interfering with its ubiquitination and proteasomal degradation. Functionally, Lys-2806 SUMOylation enabled ZFHX3-mediated cell proliferation and xenograft tumor growth of the MDA-MB-231 breast cancer cell line. These findings reveal the enzymes involved in, and the functional consequences of, ZFHX3 SUMOylation, insights that may help shed light on ZFHX3's roles in various cellular and pathophysiological processes. Full Article
ad The focal adhesion protein kindlin-2 controls mitotic spindle assembly by inhibiting histone deacetylase 6 and maintaining {alpha}-tubulin acetylation [Signal Transduction] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Kindlins are focal adhesion proteins that regulate integrin activation and outside-in signaling. The kindlin family consists of three members, kindlin-1, -2, and -3. Kindlin-2 is widely expressed in multiple cell types, except those from the hematopoietic lineage. A previous study has reported that the Drosophila Fit1 protein (an ortholog of kindlin-2) prevents abnormal spindle assembly; however, the mechanism remains unknown. Here, we show that kindlin-2 maintains spindle integrity in mitotic human cells. The human neuroblastoma SH-SY5Y cell line expresses only kindlin-2, and we found that when SH-SY5Y cells are depleted of kindlin-2, they exhibit pronounced spindle abnormalities and delayed mitosis. Of note, acetylation of α-tubulin, which maintains microtubule flexibility and stability, was diminished in the kindlin-2–depleted cells. Mechanistically, we found that kindlin-2 maintains α-tubulin acetylation by inhibiting the microtubule-associated deacetylase histone deacetylase 6 (HDAC6) via a signaling pathway involving AKT Ser/Thr kinase (AKT)/glycogen synthase kinase 3β (GSK3β) or paxillin. We also provide evidence that prolonged hypoxia down-regulates kindlin-2 expression, leading to spindle abnormalities not only in the SH-SY5Y cell line, but also cell lines derived from colon and breast tissues. The findings of our study highlight that kindlin-2 regulates mitotic spindle assembly and that this process is perturbed in cancer cells in a hypoxic environment. Full Article
ad Turkey in 2020 and Beyond: What Lies Ahead for Turkish Politics? By feedproxy.google.com Published On :: Wed, 06 Nov 2019 11:10:01 +0000 Invitation Only Research Event 25 November 2019 - 12:30pm to 1:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Fadi Hakura, Manager, Turkey Project, Europe Programme, Chatham House Turkey witnessed some major developments over the last year. In August 2018, the dramatic Lira devaluation caused the Turkish economy to go into recession. In the 2019 local elections, which took place during the economic downturn, the Republican Peoples’ Party (CHP) mayoral candidates took control of Ankara and Istanbul after 25 years of dominance by the ruling Justice and Development Party (AKP).The election results might lead to a rethink of the AKP leadership and consequences on Turkish politics will depend on Erdoğan’s interpretation of this reversal of his political fortune.Will this affect the long-standing alliance between AKP and MHP that has characterised Turkish foreign policy for the past few years? What impact will this have on both the domestic and international level? Finally, will Turkey’s recent incursion into Syria have lasting effect on the country’s alliances with other powers and its standing?In this context, the speaker will analyse the significance of these changes and the future trajectory of Turkish politics, economics and foreign policy. Event attributes Chatham House Rule Department/project Europe Programme, Turkey Project Alina Lyadova Europe Programme Coordinator Email Full Article
ad Another CDU Leadership Race Begins in Merkel’s Shadow By feedproxy.google.com Published On :: Fri, 28 Feb 2020 13:59:32 +0000 28 February 2020 Quentin Peel Associate Fellow, Europe Programme @QuentinPeel The election of a new leader of the chancellor’s party will be another contest over her legacy. 2020-02-28-Merkel.jpg German Chancellor Angela Merkel is depicted on a float in the Rosenmontag parade in Mainz on 24 February. Photo: Getty Images. Perhaps it will be second time lucky. At the end of April, Germany’s Christian Democratic Union (CDU) will elect a new party leader to follow in the footsteps of Angela Merkel. An emergency party congress has been summoned to do that after the surprise resignation of Annegret Kramp-Karrenbauer, Merkel’s chosen successor.The plan is to leave the decision on who will be the CDU candidate for chancellor at the next election until after Germany’s EU presidency concludes in December. So Merkel will keep her job until 2021, and the new leader will have to learn to live with her.The three leading candidates are Armin Laschet, Friedrich Merz and Norbert Röttgen, all from the state of North Rhine-Westphalia. Two of the three – Merz and Röttgen – were sacked by Merkel from their former jobs. They have not forgotten. Only Armin Laschet, currently CDU leader in North Rhine-Westphalia and state premier, can be described as a Merkel loyalist, true to her centrist mantra.He is the man to beat, having teamed up with Jens Spahn, the 39-year-old health minister, who is popular with party conservatives. Spahn will run as his deputy, so the team straddles the left-right divide in the party. But the contest still seems set to be a bitter battle between pro- and anti-Merkel factions that could leave the party badly split.After nearly 15 years as chancellor, and 18 years as CDU leader, Merkel remains the most popular politician in Germany. In spite of criticism that she lacks vision, her caution and predictability appear to be just what most German voters like.But her term in office has also seen the steady shrinking of the centre ground in German politics, with the rise of the environmentalist Green party and the far-right Alternative for Germany (AfD) at the expense of the centre-right CDU and the centre-left Social Democratic Party (SPD).The battle for the soul of the CDU is between those who think Merkel has been too left-wing, and want a more conservative leader to win back AfD voters, and those who believe that the CDU must stay in the centre, and prepare for a future coalition with the Greens. Merz is seen as the former, Laschet and Röttgen the latter.Unless Laschet emerges as the clear winner in April, the leadership contest is likely to leave Germany sorely distracted by domestic politics just as it takes over the EU presidency in the second half of the year. Instead of Merkel having a triumphant international swansong on the EU stage, she could be battling to protect her inheritance at home.The one area on which all three leadership candidates seem to agree is foreign policy: they all want Germany to take more leadership and responsibility, and for the European Union to play a bigger role in security, defence and international affairs. They are all Atlanticists, but critical of Donald Trump’s ‘America First’ stance. All are on the record criticizing the chancellor – at least tacitly – for not having a more vigorous foreign policy.There the similarity ends.On the right, the 64-year-old Merz is both the most conservative and the most popular with the party grassroots. He fell out with the chancellor when she took over his job as CDU leader in parliament in 2002. He quit politics to become a corporate lawyer (and a millionaire), but never lost his political ambition. He is an economic liberal but socially conservative, a strong critic of Merkel’s migration policy and her lack of clear leadership. Critics say he is a man of the past, and not a team player.On the EU, he believes Germany is ‘leaving too much to the French’. If France and Germany cannot agree on financial matters, he said at the London School of Economics in February, they should instead forge a stronger EU industrial policy focused on creating more ‘European champions’.Laschet, the Merkel loyalist, is four years younger, and from the left of the party. Like Merz, he is a former member of the European parliament. In 2015, he defended Merkel’s open border policy to accept refugees stranded in the Balkans. On Russia, however, he is more critical, calling for a new effort to re-engage with Vladimir Putin. Most recently, at the Munich Security Conference, he called for stronger Franco-German relations, and more support for the eurozone reforms proposed by Emmanuel Macron.As CDU leader in North Rhine-Westphalia, Laschet has the strongest power base. He earned his political spurs there by winning the last state election in 2017, in contrast to Röttgen, who lost to the SPD and Greens five years earlier.Röttgen, chairman of the Bundestag foreign affairs committee, is the surprise candidate. Once a Merkel favourite, they fell out when she sacked him as environment minister after he lost the North Rhine-Westphalia election. By throwing his hat in the ring, he has forced it to become an open contest. He is independent-minded and outspoken, but not as bitterly hostile to the chancellor as Merz, so he could be a compromise candidate.Laschet is clearly the man Merkel would find it easiest to live with. The decision will be taken by a party congress, not a grassroots ballot, which gives him a better chance. But Merz is the most eloquent orator and seen as the best campaigner. The challenge for party members is whether they believe it is better to swing right and squeeze the AfD, or stick to the centre to hold onto voters tempted by the Greens, who have replaced the SPD as the second-most popular party in Germany.The race is wide open. So is the future of the CDU. The only prediction one can make with much certainty is that as long as Merkel remains chancellor, any successor will struggle to get out of her shadow. Full Article
ad The heme-regulatory motifs of heme oxygenase-2 contribute to the transfer of heme to the catalytic site for degradation [Protein Structure and Folding] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Heme-regulatory motifs (HRMs) are present in many proteins that are involved in diverse biological functions. The C-terminal tail region of human heme oxygenase-2 (HO2) contains two HRMs whose cysteine residues form a disulfide bond; when reduced, these cysteines are available to bind Fe3+-heme. Heme binding to the HRMs occurs independently of the HO2 catalytic active site in the core of the protein, where heme binds with high affinity and is degraded to biliverdin. Here, we describe the reversible, protein-mediated transfer of heme between the HRMs and the HO2 core. Using hydrogen-deuterium exchange (HDX)-MS to monitor the dynamics of HO2 with and without Fe3+-heme bound to the HRMs and to the core, we detected conformational changes in the catalytic core only in one state of the catalytic cycle—when Fe3+-heme is bound to the HRMs and the core is in the apo state. These conformational changes were consistent with transfer of heme between binding sites. Indeed, we observed that HRM-bound Fe3+-heme is transferred to the apo-core either upon independent expression of the core and of a construct spanning the HRM-containing tail or after a single turnover of heme at the core. Moreover, we observed transfer of heme from the core to the HRMs and equilibration of heme between the core and HRMs. We therefore propose an Fe3+-heme transfer model in which HRM-bound heme is readily transferred to the catalytic site for degradation to facilitate turnover but can also equilibrate between the sites to maintain heme homeostasis. Full Article
ad NAD+ biosynthesis in bacteria is controlled by global carbon/nitrogen levels via PII signaling [Microbiology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 NAD+ is a central metabolite participating in core metabolic redox reactions. The prokaryotic NAD synthetase enzyme NadE catalyzes the last step of NAD+ biosynthesis, converting nicotinic acid adenine dinucleotide (NaAD) to NAD+. Some members of the NadE family use l-glutamine as a nitrogen donor and are named NadEGln. Previous gene neighborhood analysis has indicated that the bacterial nadE gene is frequently clustered with the gene encoding the regulatory signal transduction protein PII, suggesting a functional relationship between these proteins in response to the nutritional status and the carbon/nitrogen ratio of the bacterial cell. Here, using affinity chromatography, bioinformatics analyses, NAD synthetase activity, and biolayer interferometry assays, we show that PII and NadEGln physically interact in vitro, that this complex relieves NadEGln negative feedback inhibition by NAD+. This mechanism is conserved in distantly related bacteria. Of note, the PII protein allosteric effector and cellular nitrogen level indicator 2-oxoglutarate (2-OG) inhibited the formation of the PII-NadEGln complex within a physiological range. These results indicate an interplay between the levels of ATP, ADP, 2-OG, PII-sensed glutamine, and NAD+, representing a metabolic hub that may balance the levels of core nitrogen and carbon metabolites. Our findings support the notion that PII proteins act as a dissociable regulatory subunit of NadEGln, thereby enabling the control of NAD+ biosynthesis according to the nutritional status of the bacterial cell. Full Article
ad Impact of 1,N6-ethenoadenosine, a damaged ribonucleotide in DNA, on translesion synthesis and repair [Enzymology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2. Full Article
ad Quantification of the affinities of CRISPR-Cas9 nucleases for cognate protospacer adȷacent motif (PAM) sequences [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 The CRISPR/Cas9 nucleases have been widely applied for genome editing in various organisms. Cas9 nucleases complexed with a guide RNA (Cas9–gRNA) find their targets by scanning and interrogating the genomic DNA for sequences complementary to the gRNA. Recognition of the DNA target sequence requires a short protospacer adjacent motif (PAM) located outside this sequence. Given that the efficiency of target location may depend on the strength of interactions that promote target recognition, here we sought to compare affinities of different Cas9 nucleases for their cognate PAM sequences. To this end, we measured affinities of Cas9 nucleases from Streptococcus pyogenes, Staphylococcus aureus, and Francisella novicida complexed with guide RNAs (gRNAs) (SpCas9–gRNA, SaCas9–gRNA, and FnCas9–gRNA, respectively) and of three engineered SpCas9–gRNA variants with altered PAM specificities for short, PAM-containing DNA probes. We used a “beacon” assay that measures the relative affinities of DNA probes by determining their ability to competitively affect the rate of Cas9–gRNA binding to fluorescently labeled target DNA derivatives called “Cas9 beacons.” We observed significant differences in the affinities for cognate PAM sequences among the studied Cas9 enzymes. The relative affinities of SpCas9–gRNA and its engineered variants for canonical and suboptimal PAMs correlated with previous findings on the efficiency of these PAM sequences in genome editing. These findings suggest that high affinity of a Cas9 nuclease for its cognate PAM promotes higher genome-editing efficiency. Full Article
ad Non-traditional security cooperation between China and south-east Asia: implications for Indo-Pacific geopolitics By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:17:30 +0000 8 January 2020 , Volume 96, Number 1 Read online Xue Gong The ‘free and open Indo-Pacific’ (FOIP) strategy, actively promoted by the United States with support from its allies and partners, is a significant geopolitical response to China's growing power and expanding influence in Asia and beyond. Beijing has adopted various new strategies to cope with the challenges related to FOIP. One of these strategies is to secure a robust relationship with south-east Asia in order to make these regional states either neutral to or less supportive of the Indo-Pacific vision. In addition to economic statecraft and soft power, Beijing believes that it can also tap into the domain of non-traditional security (NTS) to strengthen relations with this region to position itself better in the intensifying regional geopolitical competition. The article addresses the following question: what is the impact of China's NTS cooperation with south-east Asia on Beijing's geopolitical rivalry with other major powers in the Indo-Pacific region? The article argues that China's NTS cooperation with south-east Asian countries may help China maintain its geopolitical standing in the region, but it is unlikely to lead to any dramatic increase of China's strategic influence in the region. This essentially means that Beijing may be able to prevent ASEAN or most ASEAN member states from lending substantive and strong support to the Indo-Pacific construct, but it will not be able to stop ASEAN states from supporting some elements of the FOIP. Full Article
ad The Belt and Road Initiative: geo-economics and Indo-Pacific security competition By feedproxy.google.com Published On :: Wed, 08 Jan 2020 11:58:35 +0000 8 January 2020 , Volume 96, Number 1 Read online Mingjiang Li The Belt and Road Initiative (BRI) has been regarded by international society as a major policy tool in China's geo-economic strategy. Under this policy platform, Beijing has pledged to invest billions of dollars in the infrastructure and industrial sectors across Eurasia and in the Indo-Pacific nations. It is widely believed that such huge amount of investment will inevitably generate significant geostrategic repercussions in these regions. In response to the BRI, the United States and other powers have come up with a ‘free and open Indo-Pacific’ strategy. This article attempts to address the following question: what impact is the BRI likely to have on the security ties between China and the other major players in the Indo-Pacific? The author finds that the BRI may significantly transform China's international security policy and the expansion of Beijing's security influence may further intensify the security competition between China and other major powers in the Indo-Pacific region. The article also proposes a new analytical angle for the study of geo-economics that unpacks the role of economic activities and processes in generating geopolitical intentions and catalysing geopolitical competition. Full Article
ad The Smart Peace Initiative: An Integrated and Adaptive Approach to Building Peace By feedproxy.google.com Published On :: Tue, 11 Feb 2020 10:55:01 +0000 Invitation Only Research Event 12 May 2020 - 10:00am to 11:30amAdd to CalendariCalendar Outlook Google Yahoo Smart Peace brings together global expertise in conflict analysis and research, peacebuilding and mediation programming, and behavioural science and evaluation. Together, Smart Peace partners are developing integrated and adaptive peace initiatives, working with local partners to prevent and resolve complex and intractable conflicts in Central African Republic, Myanmar and northern Nigeria. This roundtable is an opportunity for Smart Peace partners to share the Smart Peace concept, approach and objectives, and experiences of the first phases of programme implementation. Roundtable discussions among participants from policy, practice and research communities will inform future priorities and planning for Smart Peace learning, advocacy and communication. Smart Peace partners include Conciliation Resources, Behavioural Insights Team, The Centre for Humanitarian Dialogue, Chatham House, ETH Zurich, International Crisis Group and The Asia Foundation. Nilza Amaral Project Manager, International Security Programme Email Department/project International Security Programme, Smart Peace Full Article
ad Wartime paradigms and the future of western military power By feedproxy.google.com Published On :: Wed, 04 Mar 2020 13:23:13 +0000 4 March 2020 , Volume 96, Number 2 Olivier Schmitt Read Online From the perception of the imminence of threats at the political level to the seizing of initiative through proper timing at the tactical level, temporality is directly related to war and warfare. Yet, despite some analyses of the importance of time at the political/grand strategic level (usually by scholars) and at the tactical level (usually by military professionals) there is surprisingly little discussion of the impact of time on the preparation and the conduct of warfare. This article introduces the concept of ‘wartime paradigm’ as a heuristic device to understand the relationship between the perception of time and the conduct of warfare, and argues that after the Cold War, a specific ‘wartime paradigm’ combining an optimization for speed and an understanding of war as risk management has guided western warfare, from force structure to the conduct of actual operations. It shows how the changing character of warfare directly challenges this wartime paradigm and why, if western forces want to prevail in future conflicts, the establishment of a new wartime paradigm guiding technological improvements and operational concepts is critical. Full Article
ad Webinar: Director's Briefing – US Elections: The Road to November 2020 By feedproxy.google.com Published On :: Wed, 08 Apr 2020 14:50:01 +0000 Corporate Members Event Webinar Partners and Major Corporates 16 April 2020 - 1:00pm to 2:00pm Online Event participants Edward Luce, US National Editor and Columnist, Financial TimesDr Lindsay Newman, Senior Research Fellow, US and the Americas Programme, Chatham HouseChair: Dr Robin Niblett, Director and Chief Executive, Chatham House As the coronavirus crisis deepens globally, the effects have reverberated through the American economy, and in only a few short weeks, the US presidential election race has changed beyond recognition. Unemployment claims have hit unprecedented levels and look set to continue to rise with stark warnings that the worst is still to come. Polling, however, has suggested that over half the country approves of the way President Trump is handling the crisis. No issue is likely to be more important to voters come November than the recovery and rebuilding of America once the pandemic subsides. In this discussion, Ed Luce and Dr Lindsay Newman will examine the new uncertain outlook for the November 2020 election and discuss how it might play out in these challenging circumstances. Where are we versus where we thought we would be at this point in the election cycle? What should we be watching for in the coming months as the US looks to hold elections in these uncharted waters? Will the elections effectively become a referendum on Trump’s handling of the coronavirus pandemic? And what will this mean for potential policy priorities of the president?This event is only open to Major Corporate Member and Partner organizations and selected giving circles of Chatham House. If you'd like to attend, please RSVP to rsvp@chathamhouse.org. Full Article
ad The US Role in Shaping World Trade By feedproxy.google.com Published On :: Thu, 23 Apr 2020 13:45:01 +0000 Webinar Research Event 21 May 2020 - 2:00pm to 3:00pmAdd to CalendariCalendar Outlook Google Yahoo Clete Willems, Partner, Akin Gump; Deputy Director, US National Economic Council, 2018 - 19Chair: Marianne Schneider-Petsinger, Senior Research Fellow, US and Americas Programme, Chatham House This event is part of the Chatham House Global Trade Policy Forum and will take place virtually only.We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum.Please note this event is taking place between 2pm to 3pm BST. Department/project US and the Americas Programme, Global Trade Policy Forum Full Article
ad Reimagining Trade Rules to Address Climate Change in a Post-Pandemic World By feedproxy.google.com Published On :: Fri, 24 Apr 2020 10:25:01 +0000 Webinar Research Event 5 May 2020 - 2:00pm to 3:00pm Event participants James Bacchus, Distinguished University Professor of Global Affairs and Director of the Center for Global Economic and Environmental Opportunity at the University of Central Florida; Member and Chair, WTO Appellate Body, 1995 - 2003Chair: Creon Butler, Director, Global Economy and Finance Programme, Chatham House This event is part of the Chatham House Global Trade Policy Forum and will take place virtually only.International trade has a crucial role to play in tackling climate change. The production and transport of goods is a major contributor to green-house gas emissions, as is the delivery of certain cross-border services. At the same time, it looks inevitable that the COVID-19 pandemic will lead to a radical re-think of global supply chains as companies and governments seek to build in greater resilience while at the same time preserving as far as possible the efficiency gains and lower costs that global supply chains generate when operating normally.Future international trade rules will have a crucial role to play in addressing both challenges; they represent both an opportunity and a risk. If designed well, they could play a very important role in re-enforcing moves towards a more sustainable use of resources, greater overall alignment of economies with the Paris Agreement, and greater economic resilience. But they could also, if poorly designed and implemented, or overly influenced by strategic political considerations, have significant unintended and negative implications. These include: reduced economic efficiency, increased poverty, unnecessary economic decoupling and reduced consensus on the broader mitigation and adaptation measures required to meet the challenge of climate change.Against this background, a number of key questions arise: In what areas, if any, do we need to modify or adapt key principles underlying the system of global trade rules in order to respond to the twin challenges of responding to climate change and building greater economic resilience? Which are the most promising/practical areas on which trade policy experts should focus now to re-launch/re-energize discussions on WTO reform, including, for example, dispute settlement? What national economic policies will be needed to complement the development of new/reformed trade disciplines in these areas? How might future political changes, such as a change in the US administration, affect the prospects for and political momentum behind such deliberations? What in any eventuality is the best way to build the required political momentum? This roundtable is convened by the Global Economy and Finance Programme and the US and the Americas Programme and it is part of the Chatham House Global Trade Policy Forum. The event will take place virtually only.We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum.Please note this event is taking place between 2pm to 3pm BST. Department/project US and the Americas Programme, Global Trade Policy Forum Full Article
ad Virtual Roundtable: Where in the World Are We Headed? By feedproxy.google.com Published On :: Thu, 30 Apr 2020 12:20:01 +0000 Research Event 12 May 2020 - 2:00pm to 3:00pmAdd to CalendariCalendar Outlook Google Yahoo Ambassador Wendy R. Sherman, Director, Center for Public Leadership, Harvard Kennedy School; US Under Secretary of State for Political Affairs, 2011 – 2015.Lord Kim Darroch, Crossbench Life Peer, House of Lords; British Ambassador to the US, 2016 – 19Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme, Chatham House The outbreak of COVID-19 has disrupted world affairs at a time when US global leadership was already a cause of grave concern for many longstanding US partners. While the US and China have recently signed the first phase of a trade agreement, the pandemic is leading to heightened tension between these two major powers. Domestically, the virus has upended the health and economic security of many Americans during a crucial election year, and also raised genuine concern about the ability to hold a free and fair election. How will the US government navigate this unprecedented crisis and what does this mean for the future of US leadership? This event is part of the US and Americas Programme Inaugural Virtual Roundtable Series on the US and the State of the World and will take place virtually only. US and Americas Programme Email Department/project US and the Americas Programme Full Article
ad Virtual Roundtable: Evaluating Outcomes in Fragile Contexts: Adapting Research Methods in the Time of COVID-19 By feedproxy.google.com Published On :: Mon, 04 May 2020 08:55:01 +0000 Invitation Only Research Event 5 May 2020 - 12:00pm to 1:00pm Agendapdf | 107.59 KB Event participants Rebecca Wolfe, Lecturer, Harris School for Public Policy and Associate, Pearson Institute for the Study and Resolution of Global Conflicts, University of ChicagoTom Gillhespy, Principal Consultant, ItadShodmon Hojibekov, Chief Executive Officer, Aga Khan Agency for Habitat (Afghanistan)Chair: Champa Patel, Director, Asia-Pacific Programme, Chatham House This virtual roundtable has been co-convened by Chatham House and the Aga Khan Foundation. While conducting research in fragile and conflict-affected contexts has always presented challenges, the outbreak of COVID-19 creates additional challenges including travel restrictions, ethical challenges, and disruptions to usual modes of working. This virtual roundtable will explore how organizations can adapt their research and monitoring and evaluation models in response to the coronavirus pandemic. This event aims to discuss the research methods being used to mitigate the impact of the COVID-19 crisis; the important role of technology; and ways to engage policy and decision-makers during this time. Event attributes Chatham House Rule Department/project Asia-Pacific Programme, Conflict, Peace and Stability, Geopolitics and Governance Lucy Ridout Programme Administrator, Asia-Pacific Programme +44 (0) 207 314 2761 Email Full Article
ad Webinar: Director's Briefing – National Leadership in Times of Crisis By feedproxy.google.com Published On :: Thu, 07 May 2020 14:10:01 +0000 Corporate Members Event Webinar Partners and Major Corporates 14 May 2020 - 6:00pm to 7:00pmAdd to CalendariCalendar Outlook Google Yahoo Online Janet Napolitano, President, University of California; US Secretary of Homeland Security (2009-13)Chair: Dr Robin Niblett, Director and Chief Executive, Chatham House Across the globe, leaders on the local, national and international levels are grappling with the impacts of COVID-19 on their communities and the economy. But the coronavirus pandemic is just one of several existential crises the world is currently facing. Climate change, political instability and growing tensions with China and Russia, along with a lack of strong global leadership, has made it more difficult for individual nations to respond and coalesce in times of crisis.This discussion will explore how leaders at all levels can best negotiate both the practical issues and the larger questions associated with these ‘grand challenges’. How is current US foreign policy affecting our collective ability to respond to issues such as pandemics or climate change? Has the COVID-19 crisis cemented the US retreat from global leadership and if so, who might step into the breach? How do we maintain momentum on other issues in the midst of a public health disaster of this magnitude? And what is the role of the business community, higher education institutions and other sectors in responding to these crises and shaping future public policy?This event is only open to Major Corporate Member and Partner organizations and selected giving circles of Chatham House. If you'd like to attend, please RSVP to lbedford@chathamhouse.org. Full Article
ad Year Two of the Abe Administration: Prospects for the Future of Japanese Foreign Policy and UK-Japan Relations By feedproxy.google.com Published On :: Fri, 24 Jan 2014 15:29:13 +0000 Research Event 11 February 2014 - 3:00pm to 5:00pm Chatham House, London Meeting Summary: Year Two of the Abe Administration: Prospects for the Future of Japanese Foreign Policypdf | 185.89 KB Event participants Kiichi Fujiwara, Professor of International Politics, Graduate School for Law and Politics, Tokyo UniversityYuichi Hosoya, Professor of International Politics, Faculty of Law, Keio University Akiko Yamanaka, Senior Visiting Research Fellow, Churchill College, University of Cambridge; Vice Minister for Foreign Affairs of Japan (2005-2006)Chair: John Swenson-Wright, Senior Consulting Fellow, Asia Programme, Chatham House As Prime Minster Abe enters his second year in office, the speakers will consider future prospects for Japanese foreign policy and UK-Japan relations. This event is funded by the Nippon Foundation. It is held in partnership with the Nippon Foundation and the Great Britain Sasakawa Foundation.THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED. Department/project UK-Japan Global Seminar Series Full Article
ad Labour Cannot Be Complacent About UKIP’s Advance By feedproxy.google.com Published On :: Tue, 02 Sep 2014 08:38:31 +0000 2 September 2014 Professor Matthew Goodwin Visiting Senior Fellow, Europe Programme @GoodwinMJ LinkedIn Google Scholar Support for UKIP is growing among the groups in which Labour is struggling. 20140902Farage.jpg Nigel Farage speaks to voters in Clacton-on-Sea the day after Douglas Carswell MP announced he is switching allegiance from the Conservative party to UKIP. Photo by Oli Scarff/Getty Images. The UK Independence Party (UKIP) turns 21 years old this month and has cause to celebrate. The insurgent party won a national election in May and last week enjoyed the most significant coup in its history when Conservative MP Douglas Carswell defected to UKIP and announced a forthcoming by-election. Given that his coastal seat of Clacton is UKIP’s most demographically favourable seat in the country, Carswell has almost certainly handed the party its first elected member of parliament.The events in Clacton will be seen by many as validating one of the oldest myths about UKIP; that it is nothing more than a second home for disgruntled Conservatives. Carswell’s defection will be especially welcomed on the left, where many argue UKIP is dividing the right and clearing the path for Labour’s return to power in 2015. This is dangerously misguided.To understand why, we can start with Clacton. The seat has the largest concentration of the 'left behind' demographic; older, white, blue-collar voters who lack qualifications, felt excluded from Britain’s economic transformation long before the crisis, are cut adrift from politics, and are intensely anxious over the cultural as well as economic effects of migration.But as a Conservative-held seat, Clacton is also an outlier. For our book, Revolt on the Right, Robert Ford and I ranked all seats according to their demographic receptiveness to UKIP. Contrary to the prevailing wisdom, most are in Labour territory where MPs are battling with the same cocktail as Carswell: economic stagnation, unease over migration, an entrenched anti-politics consensus and anxieties over rapid social change. Of the 20 seats most demographically receptive to UKIP, 18 have Labour incumbents. Of the top 50, Labour holds 42. Of course, demography alone is not necessarily destiny. Aside from a receptive local population, UKIP also needs a favourable political context. Unlike Conservative-held seats that are at genuine risk from UKIP, Labour’s heartland seats are currently protected by large majorities.But a cursory glance at the recent European parliament results reveals the direction of travel. UKIP comfortably won the popular vote in a swath of Labour territory, and talks ambitiously of becoming the main rival to Labour in northern England. It appears to be succeeding. Across 39 local authorities in the northwest, UKIP won more votes than Labour in 13 and finished as its main rival in 23. It is similarly bleak in the northeast; across 12 authorities UKIP won the popular vote in five and finished second to Labour in seven.Since 2010, UKIP has grown fastest among the groups in which Labour is struggling most: the over-65s, the working-class and those who left education early. UKIP is tearing off this section of the electorate, creating a fundamental divide in British politics between those with the skills, education and resources to adapt, and those who have little and feel intensely angry. This is why some Ukippers talk of a '2020 strategy' and plot further advances under an Ed Miliband-led post-2015 government.Those who compare the party to earlier attempts to redraw the political map, such as the Social Democratic Party in the 1980s, or populist crusaders like the French Poujadists in the 1950s, miss a crucial point. UKIP is anchored in modern Britain’s most socially distinctive support base; it is the most working-class movement since Michael Foot’s Labour Party. Labelling UKIP as 'populist' implies that it appeals across society. It does not. Its strength is concentrated in the 'left behind', who cluster in specific geographical areas. Crucially, this is essential for success under first-past-the-post.Labour should be under no illusion. UKIP is attracting the Carswells of this world but it is also emerging as the main opposition in many northern heartlands, where it benefits from the toxicity of the Tories, moribund Labour machines that have not had to compete for decades, and the short-sightedness of some close to Ed Miliband who think only of the impact UKIP might have in 2015, and not beyond. Should UKIP’s insurgency continue, not only will it cause a rupture on the centre right, but also bring back into play Labour constituencies that have not been competitive for generations.This article was originally published in the Financial TimesTo comment on this article, please contact Chatham House Feedback Full Article
ad The Road to Gender Equality: Achievements and Challenges in China By feedproxy.google.com Published On :: Tue, 31 May 2016 14:15:01 +0000 Invitation Only Research Event 23 May 2016 - 1:00pm to 3:00pm Beijing, China Following 21 years since the adoption of the Beijing declaration by 189 states, China has the opportunity to lead the way in prioritizing gender-inclusive growth policies on the G20 agenda, as it is hosting the G20 this year.This roundtable will examine specific challenges in China, a country with a high heterogeneity in the labour force and among its population. The event will bring together representatives of government, business and civil society to continue the dialogue that Chatham House started one year ago in Beijing. Taking stock of the progress achieved so far, the participants will analyse what type of recommendations can have a positive impact in both rural and high- density populated areas.Attendance at this event is by invitation only.The Chatham House Rule To enable as open a debate as possible, this event will be held under the Chatham House Rule. Event attributes Chatham House Rule Department/project Global Economy and Finance Programme, Putting Gender Equality on the G20 Agenda Michele Bazzano Research Assistant, International Economics +44 (0)20 7314 3684 Email Full Article
ad Make It Awesome — Three Tips for Impressing Your Readers By mythicscribes.com Published On :: Mon, 04 May 2020 20:35:47 +0000 You’re a fantasy writer. You’ve created an amazing and original world, full of wondrous magic, mind-blowing monsters, and fascinating new cultures. You’ve got powerful heroes, menacing villains, and mysterious mentors. There’s just the right amount of romance. In short, you’ve got all that good stuff you’d expect to find in a fantasy novel. Only, somehow it’s still not coming out quite as awe-inspiring as you’d envisioned it. Today, I’ve got three tips for you on how to make your awesome stuff seem more awesome. Establish the Norm “When everything is awesome, awesome becomes average.” Every now and then, I come across a book that begins with the writer very obviously trying to impress me with how cool their main character is, and what an amazing world they have created, and how scary the villain is. All at once. In the first chapter. It rarely works. Let’s say there’s a ballroom full of ultra-rich and mega-powerful vampires, and then someone flies in on a golden unicorn and starts shooting fireballs the shape of grinning skulls. That would probably look rather spectacular as an introduction to a movie, but does it work in a book? Continue reading Make It Awesome — Three Tips for Impressing Your Readers at Mythic Scribes. Full Article Writing Craft & Technique
ad Marked reduction in bile acid synthesis in cholesterol 7{alpha}-hydroxylase-deficient mice does not lead to diminished tissue cholesterol turnover or to hypercholesterolemia By feedproxy.google.com Published On :: 1998-09-01 Margrit SchwarzSep 1, 1998; 39:1833-1843Articles Full Article